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INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of LEVAQUIN® and other antibacterial drugs, LEVAQUIN® should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

LEVAQUIN® Tablets/Injection and Oral Solution are indicated for the treatment of adults (≥18 years of age) with mild, moderate, and severe infections caused by susceptible strains of the designated microorganisms in the conditions listed in this section. LEVAQUIN® Injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form).

Culture and susceptibility testing

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin [see Clinical Pharmacology]. Therapy with LEVAQUIN® may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected.

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with LEVAQUIN®. Culture and susceptibility testing performed periodically during therapy will provide information about the continued susceptibility of the pathogens to the antimicrobial agent and also the possible emergence of bacterial resistance.

Nosocomial Pneumonia

LEVAQUIN® is indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see Clinical Studies].

MDRSP isolates are strains resistant to two or more of the following antibacterials: penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole.

Uncomplicated Urinary Tract Infections

LEVAQUIN® is indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.

Inhalational Anthrax (Post-Exposure)

LEVAQUIN® is indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. The effectiveness of LEVAQUIN® is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. LEVAQUIN® has not been tested in humans for the post-exposure prevention of inhalation anthrax. The safety of LEVAQUIN® in adults for durations of therapy beyond 28 days or in pediatric patients for durations of therapy beyond 14 days has not been studied. Prolonged LEVAQUIN® therapy should only be used when the benefit outweighs the risk [see Dosage and Administration (2.1, 2.2) and Clinical Studies].

DOSAGE AND ADMINISTRATION

Dosage in Adult Patients with Normal Renal Function

The usual dose of LEVAQUIN® Tablets or Oral Solution is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection and described in Table 1. The usual dose of LEVAQUIN® Injection is 250 mg or 500 mg administered by slow infusion over 60 minutes every 24 hours or 750 mg administered by slow infusion over 90 minutes every 24 hours, as indicated by infection and described in Table 1.

These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance <50 mL/min, adjustments to the dosing regimen are required [see Dosage and Administration].

1 Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies] .
2The safety of LEVAQUIN® in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [ see Warnings and Precautions (5.9), Use in Specific Populations , and Clinical Studies ] Prolonged LEVAQUIN® therapy in adults should only be used when the benefit outweighs the risk.

2.2 Dosage in Pediatric Patients

The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.

Table 2: Dosage in Pediatric Patients ≥ 6 months of age

Type of infection Due to Bacillus anthracis [ see Indications and Usage ]

Dose

Freq. Once every

DurationSequential therapy (intravenous to oral) may be instituted at the discretion of the physician.

Inhalational Anthrax (post-exposure)Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [ see Clinical Studies ]The safety of LEVAQUIN® in pediatric patients for durations of therapy beyond 14 has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [ see Warnings and Precautions, Usein Specific Populations , and Clinical Studies (14.9). ] Prolonged LEVAQUIN therapy should only be used when the benefit outweighs the risk.

Pediatric patients > 50 kg and ≥ 6 months of age

500 mg

24 hr

60 days§

Pediatric patients < 50 kg and ≥ 6 months of age

8 mg/kg (not to exceed 250 mg per dose)

12 hr

60 days§

Dosage Adjustment in Adults with Renal Impairment

Administer LEVAQUIN® with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.

No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.

In patients with impaired renal function (creatinine clearance<50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see Use in Specific Populations].

LEVAQUIN® Tablets and Oral Solution should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine chewable/buffered tablets or the pediatric powder for oral solution [see Drug Interactions and Patient Counseling Information] .

LEVAQUIN ® Injection

LEVAQUIN® Injection should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line [see Dosage and Administration].

Administration Instructions

Food and LEVAQUIN® Tablets and Oral Solution

LEVAQUIN® Tablets can be administered without regard to food. It is recommended that LEVAQUIN® Oral Solution be taken 1 hour before or 2 hours after eating.

LEVAQUIN ® Injection

Caution: Rapid or bolus intravenous infusion of LEVAQUIN® has been associated with hypotension and must be avoided. LEVAQUIN® Injection should be infused intravenously slowly over a period of not less than 60 or 90 minutes, depending on the dosage. LEVAQUIN® Injection should be administered only by intravenous infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.

Adequate hydration of patients receiving oral or intravenous LEVAQUIN® should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see Adverse Reactions and Patient Counseling Information].

2.6 Preparation of Intravenous Product

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Because only limited data are available on the compatibility of LEVAQUIN® Injection with other intravenous substances, additives or other medications should not be added to LEVAQUIN® Injection Premix in Single-Use Flexible Containers and LEVAQUIN® Injection in Single-Use Vials, or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of LEVAQUIN® Injection with an infusion solution compatible with LEVAQUIN® Injection and with any other drug(s) administered via this common line.

LEVAQUIN ® Injection in Single-Use Vials

Single-use vials require dilution prior to administration.

LEVAQUIN® Injection is supplied in single-use vials containing a concentrated levofloxacin solution with the equivalent of 500 mg (20 mL vial) and 750 mg (30 mL vial) of levofloxacin in Water for Injection, USP. The 20 mL and 30 mL vials each contain 25 mg of levofloxacin/mL. These LEVAQUIN® Injection single-use vials must be further diluted with an appropriate solution prior to intravenous administration [see Table 4 ]. The concentration of the resulting diluted solution should be 5 mg/mL prior to administration.

Compatible Intravenous Solutions: Any of the following intravenous solutions may be used to prepare a 5 mg/mL levofloxacin solution with the approximate pH values:

Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparation of the final intravenous solution. Since the vials are for single-use only, any unused portion remaining in the vial should be discarded. When used to prepare two 250 mg doses from the 20 mL vial containing 500 mg of levofloxacin, the full content of the vial should be withdrawn at once using a single-entry procedure, and a second dose should be prepared and stored for subsequent use [see Stability of LEVAQUIN® Injection Following Dilution ] .

Prepare the desired dosage of levofloxacin according to Table 5:

Table 5: Preparation of LEVAQUIN® Intravenous Solution

Desired Dosage Strength

From Appropriate Vial, Withdraw Volume

Volume of Diluent

Infusion Time

250 mg

10 mL (20 mL Vial)

40 mL

60 min

500 mg

20 mL (20 mL Vial)

80 mL

60 min

750 mg

30 mL (30 mL Vial)

120 mL

90 min

For example, to prepare a 500 mg dose using the 20 mL vial (25 mg/mL), withdraw 20 mL and dilute with a compatible intravenous solution to a total volume of 100 mL.

This intravenous drug product should be inspected visually for particulate matter prior to administration. Samples containing visible particles should be discarded.

Stability of LEVAQUIN® Injection Following Dilution: LEVAQUIN® Injection, when diluted in a compatible intravenous fluid to a concentration of 5 mg/mL, is stable for 72 hours when stored at or below 25°C (77°F) and for 14 days when stored under refrigeration at 5°C (41°F) in plastic intravenous containers. Solutions that are diluted in a compatible intravenous solution and frozen in glass bottles or plastic intravenous containers are stable for 6 months when stored at - 20°C (- 4°F). Thaw frozen solutions at room temperature 25°C (77°F) or in a refrigerator 8°C (46°F). Do not force thaw by microwave irradiation or water bath immersion. Do not refreeze after initial thawing.

LEVAQUIN® Injection is also supplied in flexible containers within a foil overwrap. These contain a premixed, ready to use levofloxacin solution in 5% dextrose (D5W) for single-use. The 100 mL premixed flexible containers contain either 250 mg/50 mL or 500 mg/100 mL of levofloxacin solution. The 150 mL flexible container contains 750 mg/150 mL of levofloxacin solution. The concentration of each container is 5 mg/mL. No further dilution of these preparations is necessary.Because the premix flexible containers are for single-use only, any unused portion should be discarded.

Instructions for the Use of LEVAQUIN® Injection Premix in Flexible Containers:

Tear outer wrap at the notch and remove solution container.

Check the container for minute leaks by squeezing the inner bag firmly. If leaks are found, or if the seal is not intact, discard the solution, as the sterility may be compromised.

Do not use if the solution is cloudy or a precipitate is present.

Use sterile equipment.

WARNING: Do not use flexible containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

Preparation for Administration:

Close flow control clamp of administration set.

Remove cover from port at bottom of container.

Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton.

LEVAQUIN® (levofloxacin in 5% dextrose) Injection is supplied as a single-use, premixed solution in flexible containers. Each bag contains a dilute solution with the equivalent of 250, 500, or 750 mg of levofloxacin, respectively, in 5% Dextrose (D5W).